Several tn homozygous mouse embryos are being studied so that the cause of lethality of the alleles at the T-locus can be determined. Two preimplantation lethal homozygotes (tw32 and t12) and an implantation lethal homozygote (t6) are being investigated. Common ultrastructural characteristics, i.e. binucleate cells, and excessive lipid, together with reduced energy metabolism prior to developmental arrest in all three mutants, suggest that the lethal effect of the various alleles is related to defective intermediary metabolism. This defect results in reduced ATP synthesis at the developmental stage prior to death. Excessive lipid droplets and binucleate cells are found concomitantly with the depressed ATP synthesis. Prior to the stage at which the mutants show a reduced rate of ATP synthesis, these same embryos synthesize greater amounts of ATP than their wild-type counterparts. Our studies have been extended to tn-bearing spermatozoa which exhibit meiotic drive. Preliminary data suggest that this phenomenon results from excessive metabolism. Our research is designed to determine the level of this metabolic error in aerobic respiration. The methods used include ultrastructural, autoradiographic and biochemical techniques.